Healing Chronic Wounds With Protein
Wound Healing Consists of Four Interconnected Steps
The wound healing process consists of 4 interconnected steps; hemostasis, inflammation, proliferation and tissue remodeling. Wounds that fail to properly progress through these steps result in delayed wound healing or the formation of chronic wounds. These chronic wounds are often stuck in a “state of inflammation.” Most chronic wounds develop as a result of diabetes, tissue ischemia, venous stasis and/or tissue pressure.
During wound healing, after bleeding is controlled, inflammatory cells (neutrophils, macrophages and lymphocytes) migrate into the wound area. The neutrophils battle invading bacteria and clear cellular debris. Macrophages produce cytokines that attract leukocytes to the wound and clear dead cells. T-lymphocytes populate the wound during the proliferation and remodeling stage playing a major role in ultimate tissue integrity. The body’s immune response is critical for the wound healing process.
Nutrition has been noted to have a major impact on wound healing.
However, this is much more than “eating your greens and beans.” Protein has been identified as a critical macronutrient. Protein needs for chronic wound healing appear to be much higher than previously believed. Protein deficiency can impair capillary function, fibroblast proliferation, collagen synthesis and wound remodeling. Protein deficiency can also impair immune function.
Two specific proteins are of special interest, arginine and glutamine. Both have unique properties that can promote proper wound healing.
Arginine is a semi-essential amino acid. It is a precursor to proline which is imperative for collagen formation, angiogenesis and wound contraction to support proper wound healing. Arginine also supports the overall immune response. Arginine is metabolized to nitrous oxide, a signal molecule for proper immune response, angiogenesis, epithelialization and granulation. Arginine is also metabolized to ornithine, an essential precursor for collagen formation.
Glutamine is the most abundant amino acid in human plasma. It is a major source of energy for rapid cell growth and proliferation, especially fibroblasts, epithelial cells and macrophages. Glutamine promotes nitrogen retention and muscle protein synthesis. Glutamine appears to play a crucial role during the initial inflammatory stage of wound healing.
There have been a few trials evaluating the use of arginine and glutamine on wound healing. These amino acids were combined with B-hydroxy-B-methylbutarate (HMB) a naturally occurring metabolite of leucine which can inhibit muscle proteolysis and modulate protein turnover.
A prospective, randomized study of normal volunteers randomized to arginine, glutamine and HMB or placebo after experimental wound creation demonstrated a significant increase in wound collagen formation in the supplemented group.1 A retrospective, observational analysis of supplementation of arginine, glutamine and HMB in diabetic dialysis patients with foot wounds demonstrated a maintenance or improvement in wound healing.2 Another, retrospective, observational study evaluated the use of arginine, glutamine and HMB as an oral supplement in patients with recurrent, diabetic foot ulcers that were neuropathic in origin. They compared wound healing outcomes with the oral supplement as compared to the original wound healing outcomes. Arginine, glutamine and HMB supplementation resulted in reduced antibiotic usage, reduced healing-associated costs and a reduction in time to healing.3
Nutrition is a critical component of proper wound healing, especially protein. We have previously written about the importance of protein delivered at higher levels than previously considered for the healing of chronic wounds. The use of supplemental arginine and glutamine for improvement in wound healing is a provocative option. Supplemental intravenous glutamine and arginine are not currently FDA approved in the United States. Their use as a protein supplement and for their pharmacologic effects on wound healing would be an important area of clinical research for the future.
Dr. DeLegge Bio
Dr. DeLegge is board certified in internal medicine, gastroenterology and nutrition. He manages patients with complex medical problems such as malabsorption and short bowel syndrome. He also is the specialist for placement of feeding tubes in the gastrointestinal tract, and the subsequent management of those patients. His nutrition research focuses on nutritional assessment, parenteral nutrition and enteral nutrition.
Mark DeLegge, MD
Professor of Medicine
Medical University of South Carolina
1. Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg 2002;236:369-375.
2. Sipahi S, Gungor O, Gunduz M, et al. the effect of oral supplementation with a combination of B-hydroxy-B-methylbuturate, arginine and glutamine on wound healing: a retrospective study of hemodialysis patients. BMC Nephro 2013;14:8-12.
3. Tatti P, Barber AE. The use of specialized nutritional supplementation for diabetic foot ulcers reduces the use of antibiotics. J Endocrinol Metab 2012;12:26-31.